KR20190108362A - Skin absorption functional material using dermal penetration peptide - Google Patents

Abstract

The present invention relates to a skin absorption functional composition using DPP. More specifically, the present invention relates to the skin absorption functional composition using DPP which increases cell permeability by using a molecular peptide material, which is a functional material to combine with high molecular weight materials for skin improvement for transferring a material to the dermis, thereby improving absorptive power. According to the skin absorption functional composition using DPP of the present invention, a delivery material (growth factor and the like) can be evenly delivered to the dermis and an effect occurs that DPP effectively delivers the delivery material, so that the delivery material hardly remains on the epidermis.

Description

Skin absorption functional composition using DPP {SKIN ABSORPTION FUNCTIONAL MATERIAL USING DERMAL PENETRATION PEPTIDE}

The present invention relates to a skin absorption functional composition using DPP, and more particularly, by using a molecular peptide material, which is a functional material, combines with a high molecular weight material for skin improvement by transporting a substance to the dermis by increasing cell penetration. It relates to a skin absorption functional composition using DPP to increase the absorption.

The skin is a tissue that is always in contact with the outside environment. Its main function is to protect body fluids from leakage and infection, as well as act as a protective barrier against water loss. The stratum corneum of the epidermis is located on the outermost surface of the skin and prevents the skin from drying out by inhibiting the loss of moisture and electrolytes outside the skin, and provides an environment for normal biochemical metabolism of the skin. It protects the human body from humans and plays an important role in preventing bacteria, fungi, viruses, etc. from invading the skin (Bouwstra J. A, Honeywell-Nguyen PL Gooris GS and Ponec M. Prog Lipid Res. 42: 1-36 (2003)).

There are three pathways for absorption through the skin, through the stratum corneum, through the hair follicle and sebaceous glands, and through the sweat glands (Prausnitz M. R. and Langer R. Nat Biotech. 26: 1261-1268 (2008)). The delivery of physiologically active molecules through the skin is subject to various limitations due to the structural and physical properties of the skin. To date, absorption through the stratum corneum is known as the most important absorption pathway. In particular, the stratum corneum of the skin is keratinocyte (the major constituent cell of the skin) is natural death and forms a dense structure in the outermost layer of the skin, inhibits the evaporation of moisture as well as the penetration of foreign substances, sweat and various lipid components Due to the acidity is showing around pH 5. In order to penetrate the stratum corneum barrier, the molecular weight must be as small as 1,000 or less and possess lipophilic properties (Metha R. C. and Fitzpatrick R. E. Dermatol. Ther. 20: 350-359 (2007)).

It is known that low molecular weight synthetic compounds and natural compounds with a molecular weight of 1,000 or less that are frequently used as cosmetic ingredients can be easily transferred into cells, but macromolecules such as proteins, peptides and nucleic acids with molecular weight of 1,000 or more have a double lipid membrane structure due to their molecular weight. It is difficult to penetrate into the cell membrane. In fact, due to the intrinsic properties of the stratum corneum, which constitutes the skin barrier, they are known to have extremely low permeation efficiency of low molecular weight materials and lower permeation efficiency of high molecular weight materials.

As a method for amplifying the efficiency of such small molecules and macromolecules to cross the plasma membrane of the cell, a recent interest is the method of transdermal drug delivery (TDD) (Prausnitz MR and Langer R. Nat Biotech. 26: 1261-1268 (2008).

However, the biggest barrier of the method of administration through the skin is keratinocytes in the stratum corneum and keratinocyte lipids therebetween. The molecules that are physiologically active in most skin (hereafter, skin bioactive molecules) are transdermal because of the resistance of the stratum corneum.

The transmittance becomes low.

Various methods for promoting the percutaneous permeability of such skin bioactive molecules have been studied, which can be roughly divided into physical, biochemical, and chemical methods. The physical method is mainly using iontophoresis, electroporation, sonophoresis, and thermal ablation. The biochemical method uses precursors to activate active ingredients during and after the skin. The chemical method is the most widely used method in the industry, and various kinds of bases, surfactants, solvents, and fatty acids are mainly in the form of complexes carrying bioactive molecules. Carrier-mediated delivery systems are being used (Prausnitz MR and Langer R. Nat Biotech. 26: 1261-1268 (2008)). Among these, much attention has recently been focused on the use of peptide-based delivery systems.

The use of peptides having cell permeability has several advantages, mainly due to the various modifications that can be made to the peptide sequence at all times. It can designate different subcellular domains and allow the manipulation of carriers that can carry various forms of cargo molecules.

Techniques for absorbing the high molecular weight material have been disclosed in the Republic of Korea Patent Publication No. 13993397.

However, the conventional transdermal delivery material delivery system has the following problems.

(1) It delivers the necessary substances, but its energy is insufficient to spread evenly enough to the lower part of the dermis.

(2) Due to the lack of energy in the necessary substances, the rate of passage through the epidermis is low, leaving high molecular weight substances in the skin.

In order to solve the above problems, the present invention is a composition for transdermal delivery comprising a DLP (Dermal Penetration Peptide) molecule is bound to the intracellular molecular transport peptide,

It provides a composition characterized in that the peptide has an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 3.

According to the skin absorption functional composition using the DPP of the present invention the following effects occur.

(1) It can evenly deliver the necessary substances to the dermis as shown in FIG.

(2) DPP delivers the delivery material very well, so there is very little leftover in the epidermis.

1 is a dermal delivery concept of the skin absorption functional composition using DPP formed as a preferred embodiment of the present invention.
Figure 2 is a conceptual diagram showing the experimental results of the skin absorption functional composition using DPP formed in a preferred embodiment of the present invention.

The present invention is understood that exosomes formed of small size (30-150 nm) vesicles containing sophisticated RNA and protein carriers are specifically secreted for the purpose of transmitting signals between cells. The idea was to create a delivery material.

The exosomes (Exosome) is a biological nanoparticles of 30 ~ 100nm size secreted by most eukaryotic cells, and contains information consisting of proteins, lipids, such as DNA, RNA, peptides and the like.

The exosomes secreted into the blood by the cells are surrounded by a lipid structure membrane, which can safely transport the substances from the enzymes in the blood, and transmit information to and communicate with adjacent cells or distant cells. It also affects the environment.

Endosomal sorting complex required for trasport (ESCRT) protein plays an important role in the production of the exosomes. The ESCRT protein can be analyzed to isolate domains that play an important role in vesicle transportation.

The ESCRT is composed of four proteins of ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Each of these four proteins is divided into 10-20 amino acids in the keratinocytes. Flow cytometry was used to confirm the in vitro cell permeability of the luminescent bodies in the cells (see FIG. 2).

In addition, the skin permeability of artificial skin tissue was confirmed using EpiDerm (MatTek, USA) for the analysis of the permeability of the stratum corneum in Ex vivo tissue, and the optimized skin permeation amino acid sequence through skin permeation test using porcine skin To derive the sequence number of the present invention was devised.

The present invention provides a composition for transdermal delivery comprising a DPP (Transdermal Peptide) molecule to which intracellular molecular transport peptides are bound, wherein the peptide has an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 3 to provide.

<Sequence>

1) DPP-1: H-HTVPAPIPCCAA-NH2

2) DPP-2: H-AVTGGAQHPCG-NH2

3) DPP-3: H-MATGPPQHQPG-NH2

According to the skin absorption functional composition using the DPP of the present invention, it is possible to evenly deliver the delivery material (growth factor, etc.) to the dermis, and the DPP delivers the delivery material well and hardly remains in the epidermis.

Although the present invention has been described with reference to the accompanying drawings, it will be apparent to those skilled in the art that various modifications may be made without departing from the scope of the invention as defined by the following claims.

Claims (3)

A transdermal delivery composition comprising DPP (Dermal Penetration Peptide) molecules bound to intracellular molecular transport peptides, wherein the peptide (DPP-1) has an amino acid sequence consisting of H-HTVPAPIPCCAA-NH2 Absorption functional composition. A composition for transdermal delivery comprising DPP (Dermal Penetration Peptide) molecules bound to intracellular molecular transport peptides, wherein the peptide (DPP-2) has an amino acid sequence consisting of H-AVTGGAQHPCG-NH2 Absorption functional composition. A transdermal delivery composition comprising DPP (Dermal Penetration Peptide) molecules bound to intracellular molecular transport peptides, wherein the peptide (DPP-3) has an amino acid sequence consisting of H-MATGPPQHQPG-NH2 Absorption functional composition.

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